oxymorphone and Kidney-Failure--Chronic

The pharmacokinetics of oxycodone in patients with end-stage renal disease (ESRD) requiring haemodialysis are largely unknown. Therefore, we investigated the pharmacokinetics of oxycodone/naloxone prolonged release and their metabolites in patients with ESRD during and between haemodialysis sessions.. Single doses of oxycodone/naloxone (5/2.5 or 10/5 mg) were administered in nine patients with ESRD using a cross-over design on the day of dialysis and on a day between dialysis sessions. Plasma, dialysate and urine concentrations of oxycodone, naloxone and their metabolites were determined up to 48 h post-dosing using a liquid chromatography-tandem mass spectrometry system.. Haemodialysis performed 6-10 h after dosing removed ∼10% of the administered dose of oxycodone predominantly as unconjugated oxycodone and noroxycodone or conjugated oxymorphone and noroxymorphone. The haemodialysis clearance of oxycodone based on its recovery in dialysate was (mean ± SD) 8.4 ± 2.1 L/h. The geometric mean (coefficient of variation) plasma elimination half-life of oxycodone during the 4-h haemodialysis period was 3.9 h (39%) which was significantly shorter than the 5.7 h (22%) without haemodialysis. Plasma levels of the active metabolite oxymorphone in its unconjugated form were very low.. Oxycodone is removed during haemodialysis. The pharmacokinetics including the relatively short half-life of oxycodone in patients with ESRD with or without haemodialysis and the absence of unconjugated active metabolites indicate that oxycodone can be used at usual doses in patients requiring dialysis.

Topics: Adult; Aged; Analgesics, Opioid; Cross-Over Studies; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Morphinans; Naloxone; Narcotic Antagonists; Oxycodone; Oxymorphone; Prognosis; Renal Dialysis; Tissue Distribution

Prescription opioid abuse poses a serious problem in the United States, representing 615 per 100 000 deaths annually. Extended-release oxymorphone (Opana-ER) is an oral opioid pain medication that has recently been found to cause thrombotic microangiopathy when intravenously abused. In this retrospective study, we attempted to determine the prevalence and outcomes of acute kidney injury (AKI) among patients intravenously abusing extended-release oral oxymorphone.. A query of electronic medical records for 'drug abuse' at an academic medical centre during January 2012 to December 2015 was performed and yielded 2350 patients. Patients were further identified by documented intravenous abuse of extended-release oxymorphone. Patients were stratified based on multiple renal indices and outcomes. Potential confounders were also identified.. One hundred and sixty-five patients were found to have a documented history of intravenous abuse of extended-release oral oxymorphone. Prevalence of AKI in this population was a 47.8%. KDIGO stage-I patients consisted of 17.8% of patients with AKI, 40.5% were classified as KDIGO stage-II AKI, and 41.8% were classified as KDIGO stage-III AKI. Among patients with AKI, average age was found to be 37.5 years, 59.4% experienced renal recovery, 56.9% required intensive care unit admission, 13.9% progressed to end-stage renal disease (ESRD), and 7.6% expired during admission.. Clinicians should be educated to help recognize intravenous abuse of extended-release oral oxymorphone and its associated effects. Our data suggests AKI is common in these patients; higher KDIGO staging appears to be associated with slower rates of renal recovery, increased comorbidities and progression to both CKD and ESRD.

Topics: Acute Kidney Injury; Administration, Oral; Analgesics, Opioid; Comorbidity; Delayed-Action Preparations; Disease Progression; Drug Compounding; Female; Hospital Mortality; Humans; Injections, Intravenous; Kidney; Kidney Failure, Chronic; Male; Middle Aged; North Carolina; Opioid-Related Disorders; Oxymorphone; Prevalence; Recovery of Function; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Substance Abuse, Intravenous; Time Factors

Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking.. We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis.. Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased.. While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.

Topics: Adult; Analgesics, Opioid; Chronic Disease; Chronic Pain; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Morphinans; Oxycodone; Oxymorphone; Renal Dialysis

The use of opioid analgesics in renal dysfunction is potentially problematic and many patients with end stage renal disease are unable to tolerate these medications. A greater understanding of the pharmacokinetics of opioid analgesics is vital in informing safe and effective practice. Using pharmacokinetic analysis, this case study demonstrates for the first time that oxycodone and its metabolites are removed by haemodialysis. As such, care should be taken when using oxycodone in patients undergoing haemodialysis.

Topics: Analgesics, Opioid; Female; Humans; Kidney Failure, Chronic; Middle Aged; Morphinans; Nephrectomy; Oxycodone; Oxymorphone; Renal Dialysis